CaMKII activation state underlies synaptic labile phase of LTP and short-term memory formation.
BACKGROUND
The labile state of short-term memory has been known for more than a century. It has been frequently reported that immediate postlearning intervention can readily disrupt newly formed memories. However, the molecular and cellular mechanisms underlying the labile state of new memory are not understood.


RESULTS
Using a bump-and-hole-based chemical-genetic method, we have rapidly and selectively manipulated alpha CaMKII activity levels in the mouse forebrain during various stages of the short-term memory processes. We find that a rapid shift in the alpha CaMKII activation status within the immediate 10 min after learning severely disrupts short-term memory formation. The same manipulation beyond the 15 min after learning has no effect, suggesting a critical time window for CaMKII action. We further show that during this same 10 min time window only, shifting in CaMKII activation state is capable of altering newly established synaptic weights and/or patterns.


CONCLUSIONS
The initial 10 min of memory formation and long-term potentiation are sensitive to inducible genetic upregulation of alphaCaMKII activity. Our results suggest that molecular dynamics of CaMKII play an important role in underlying synaptic labile state and representation of short-term memory during this critical time window.
Wang
Huimin
H
Brain and Behavior Discovery Institute, Medical College of Georgia, Augusta, Georgia 30912, USA.
Feng
Ruiben
R
Phillip Wang
L
L
Li
Fei
F
Cao
Xiaohua
X
Tsien
Joe Z
JZ
D000818:Animals; D001522:Behavior, Animal; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D003213:Conditioning, Psychological; D004594:Electrophysiology; D005239:Fear; D015870:Gene Expression; D006624:Hippocampus / Q000201:enzymology / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology*; D008570:Memory, Short-Term / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D021641:Recognition, Psychology; D012153:Retention, Psychology; D013997:Time Factors
C479693:1-tert-butyl-3-naphthalen-1-ylmethyl-1H-pyrazolo(3,4-d)pyrimidin-4-ylemine; D011720:Pyrazoles; D011743:Pyrimidines; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2